Clinical Relevance of Serum Full-Length Glypican-3 in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab and Bevacizumab

Biomarkers that predict survival and therapeutic response to atezolizumab plus bevacizumab (Atezo/Bev) in unresectable hepatocellular carcinoma (HCC) have yet to be established. We aimed to investigate the association between serum full-length glypican-3 (FL-GPC3) concentration and treatment outcomes in patients with unresectable HCC receiving Atezo/Bev. We included 102 patients treated with Atezo/Bev therapy for unresectable HCC at our institute during 2020–2025. We investigated the association between baseline serum FL-GPC3 concentrations and the therapeutic effectiveness and survival outcomes. The baseline serum FL-GPC3 concentration was lower in patients in whom disease control was achieved (10.8 vs. 26.7 pg/mL, p = 0.002). An FL-GPC3 concentration ≥ 21.7 pg/mL was an independent negative predictor of disease control (odds ratio, 0.377; 95% confidence interval [CI], 0.148–0.963; p = 0.042). The FL-GPC3-high group had a shorter median progression-free survival (PFS; 3.0 vs. 5.6 months, p = 0.031) and overall survival (OS; 13.7 vs. 25.8 months, p = 0.006) than the FL-GPC3-low group. A high FL-GPC3 concentration was an independent negative prognostic factor for PFS (hazard ratio [HR], 1.567; 95% CI, 1.025–2.396; p = 0.038) and OS (HR, 1.694; 95% CI, 1.003–2.862; p = 0.049). In conclusion, baseline serum FL-GPC3 concentration was associated with treatment outcomes in patients with unresectable HCC receiving Atezo/Bev and may provide complementary prognostic information.